This is a phase I, single-center, open-label, inter-patient dose escalation toxicity study of new gene therapy for malignant gliomas. Our hypothesis is that the local production of interferon-b by gene delivery within a brain tumor will results in high intratumoral levels of this cytokine with low systemic and low global CNS exposure. The interferon is known to induce tumor cell apoptosis and in experimental models is able to completely eradicate tumors. The primary objective is to determine the toxicity of intratumoral injection of recombinant adenovirus expressing human interferon-beta (H5.010CMVhIFN-b ) in patients with recurrent or progressive malignant glioma and to determine the maximum tolerated dose of H5.010CMVhIFN-b. Our secondary objectives are to (1) assess the relationship between the dose of H5.010CMVhIFN-b in patients with recurrent or progressive malignant glioma and the clinical/biological response as assessed by physical examination, MRI scan, and survival; the pathologic evidence of gene transfer in resected tumor specimens; (2) determine serum, cerebrospinal fluid and brain interferon-beta levels; and (3) determine the immune response to adenoviral vector and/or human interferon-beta. Approximately 18 to 21 subjects aged 18 to 75, inclusive, with a diagnosis of recurrent or progressive malignant glioma, with tumor that is amenable to surgical resection will be enrolled.